title: Macrophages lift off surface-bound bacteria using a filopodium-lamellipodium hook-and-shovel mechanism.
abstract: To clear pathogens from host tissues or biomaterial surfaces, phagocytes have to break the adhesive bacteria-substrate interactions. Here we analysed the mechanobiological process that enables macrophages to lift-off and phagocytose surface-bound Escherichia coli (E. coli). In this opsonin-independent process, macrophage filopodia hold on to the E. coli fimbriae long enough to induce a local protrusion of a lamellipodium. Specific contacts between the macrophage and E. coli are formed via the glycoprotein CD48 on filopodia and the adhesin FimH on type 1 fimbriae (hook). We show that bacterial detachment from surfaces occurrs after a lamellipodium has protruded underneath the bacterium (shovel), thereby breaking the multiple bacterium-surface interactions. After lift-off, the bacterium is engulfed by a phagocytic cup. Force activated catch bonds enable the long-term survival of the filopodium-fimbrium interactions while soluble mannose inhibitors and CD48 antibodies suppress the contact formation and thereby inhibit subsequent E. coli phagocytosis.
authors.affiliation: Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Möller
authors.forename: Tessa
authors.initials: T
authors.lastname: Lühmann
authors.forename: Mamta
authors.initials: M
authors.lastname: Chabria
authors.forename: Heike
authors.initials: H
authors.lastname: Hall
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D018830:Adhesins, Escherichia coli / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001422:Bacterial Adhesion / Q000276:immunology*; D000071178:CD48 Antigen; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000502:physiology / Q000648:ultrastructure; D036781:Fimbriae Proteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology* / Q000648:ultrastructure; D008954:Models, Biological; D010587:Phagocytosis / Q000276:immunology; D011554:Pseudopodia / Q000502:physiology*; D033081:Shear Strength
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C058769:fimH protein, E coli; D036781:Fimbriae Proteins